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TNF-related apoptosis-inducing ligand (TRAIL) in HIV-1-infected patients and its in vitro production by antigen-presenting cells

  1. Author:
    Herbeuval, J. P.
    Boasso, A.
    Grivel, J. C.
    Hardy, A. W.
    Anderson, S. A.
    Dolan, M. J.
    Chougnet, C.
    Lifson, J. D.
    Shearer, G. M.

  2. Author Address

    Shearer, GM, NCI, Expt Immunol Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Henry M Jackson Fdn & Infect Dis Serv, Wilford Hall USAF Med Ctr, Lackland AFB, TX USA. Childrens Hosp Res Fdn, Div Mol Immunol, Cincinnati, OH 45229 USA. NCI, AIDS Vaccine Program, Sci Applicat Int Corp, Frederick, MD 21701 USA.
    1. Year: 2005
  2. Journal: Blood
    1. 105
    2. 6
    3. Pages: 2458-2464
  4. Type of Article: Meeting Abstract
  1. Abstract:

    There is now considerable in vitro evidence that tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is involved in HIV-1 pathogenesis by inducing CD4(+) T-cell death characteristic of AIDS. Therefore, we have tested levels of TRAIL in plasma samples from 107 HIV-1-infected and 53 uninfected controls as well as in longitudinal plasma samples from patients who started antiretroviral therapy (ART). TRAIL was elevated in plasma of HIV-1-infected patients compared with uninfected individuals, and patients receiving ART showed decreased plasma TRAIL levels that correlated with reduction in viral load. In vitro exposure to infectious and noninfectious HIV-1 induced TRAIL in monocytes and marginally in dendritic cells (DCs) but not in macrophages or T cells. Interestingly, the HIV-1 entry inhibitor, soluble CD4, blocked HIV-1-induced production of TRAIL. Furthermore, production and gene expression of TRAIL by monocytes were regulated by type I interferon via signal transducer and activator of transcription-1 (STAT1)/STAT2 signaling molecule. Ex vivo HIV-1 infection of human tonsil lymphoid tissue also resulted in increased TRAIL production. We demonstrate here that plasma TRAIL is elevated in HIV-1-infected patients and is decreased by ART therapy. The high production of TRAIL by antigen-presenting cells may contribute to the death of CD4(+) T cells during progression to AIDS. (c) 2005 by The American Society of Hematology

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External Sources

  1. View record in Web of Science®
  2. WOS: 000227630500043

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